Preben Bo Mortensen

Association of Whole-Genome and NETRIN1 Signaling Pathway-Derived Polygenic Risk Scores for Major Depressive Disorder and White Matter Microstructure in the UK Biobank

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Miruna C Barbu, University of Edinburgh, Storbritannien
  • Yanni Zeng, University of Edinburgh, Storbritannien
  • Xueyi Shen, University of Edinburgh, Storbritannien
  • Simon R Cox, University of Edinburgh, Storbritannien
  • Toni-Kim Clarke, University of Edinburgh, Storbritannien
  • Jude Gibson, University of Edinburgh, Storbritannien
  • Mark J Adams, University of Edinburgh, Storbritannien
  • Mandy Johnstone, University of Edinburgh, Storbritannien
  • Chris S Haley, University of Edinburgh, Storbritannien
  • Stephen M Lawrie, University of Edinburgh, Storbritannien
  • Ian J Deary, University of Edinburgh, Storbritannien
  • Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
  • ,
  • 23andMe Research Team
  • ,
  • Andrew M McIntosh, University of Edinburgh, Storbritannien
  • Heather C Whalley, University of Edinburgh, Storbritannien

BACKGROUND: Major depressive disorder is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome and have reported growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide important routes for identification of disease mechanisms by focusing on a specific process, excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether major depressive disorder polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRSs) and the whole genome, excluding NETRIN1 pathway genes (genomic-PRSs), were associated with white matter microstructure.

METHODS: We used two diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK Biobank neuroimaging data release (FA: n = 6401; MD: n = 6390).

RESULTS: We found significantly lower FA in the superior longitudinal fasciculus (β = -.035, pcorrected = .029) and significantly higher MD in a global measure of thalamic radiations (β = .029, pcorrected = .021), as well as higher MD in the superior (β = .034, pcorrected = .039) and inferior (β = .029, pcorrected = .043) longitudinal fasciculus and in the anterior (β = .025, pcorrected = .046) and superior (β = .027, pcorrected = .043) thalamic radiation associated with NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in several tracts.

CONCLUSIONS: Our findings indicate that variation in the NETRIN1 signaling pathway may confer risk for major depressive disorder through effects on a number of white matter tracts.

OriginalsprogEngelsk
TidsskriftBiological psychiatry. Cognitive neuroscience and neuroimaging
Vol/bind4
Nummer1
Sider (fra-til)91-100
Antal sider10
ISSN2451-9022
DOI
StatusUdgivet - 2019

Se relationer på Aarhus Universitet Citationsformater

ID: 133205116